HUMORAL AND INTRACARDIAC
MECHANISMS OF HEART’ REGULATION.
In humans and other
mammals, multiple cardiovascular regulatory mechanisms have evolved. These
mechanisms increase the blood supply to active tissues and increase or decrease
heat loss from the body by redistributing the blood. In the face of challenges
such as hemorrhage, they maintain the blood flow to the heart and brain. When
the challenge faced is severe, flow to these vital organs is maintained at the
expense of the circulation to the rest of the body.
Circulatory adjustments
are effected by altering the output of the pump (the heart), changing the
diameter of the resistance vessels (primarily the arterioles), or altering the
amount of blood pooled in the capacitance vessels (the veins). Regulation of
cardiac output is discussed in Chapter 29. The caliber of the arterioles is adjusted in part
by autoregulation. It is also increased in active tissues by locally produced
vasodilator metabolites, is affected by substances secreted by the endothelium,
and is regulated systemically by circulating vasoactive substances and the
nerves that innervate the arterioles. The caliber of the capacitance vessels is
also affected by circulating vasoactive substances and by vasomotor nerves. The
systemic regulatory mechanisms synergize with the local mechanisms and adjust
vascular responses throughout the body.
The terms vasoconstriction
and vasodilation are generally used to refer to constriction and
dilation of the resistance vessels. Changes in the caliber of the veins are
referred to specifically as venoconstriction or venodilation.
Autoregulation
The capacity of tissues
to regulate their own blood flow is referred to as autoregulation. Most
vascular beds have an intrinsic capacity to compensate for moderate changes in
perfusion pressure by changes in vascular resistance, so that blood flow
remains relatively constant. This capacity is well developed in the kidneys
(see Chapter 38), but it has also been observed in the mesentery,
skeletal muscle, brain, liver, and myocardium. It is probably due in part to
the intrinsic contractile response of smooth muscle to stretch (myogenic
theory of autoregulation). As the pressure rises, the blood vessels are
distended and the vascular smooth muscle fibers that surround the vessels
contract. If it is postulated that the muscle responds to the tension in the
vessel wall, this theory could explain the greater degree of contraction at
higher pressures; the wall tension is proportionate to the distending pressure
times the radius of the vessel (law of Laplace; see Chapter 30), and the maintenance of a given wall tension as the
pressure rises would require a decrease in radius. Vasodilator substances tend
to accumulate in active tissues, and these "metabolites" also
contribute to autoregulation (metabolic theory of autoregulation). When
blood flow decreases, they accumulate and the vessels dilate; when blood flow
increases, they tend to be washed away.
Vasodilator
Metabolites
The metabolic changes
that produce vasodilation include, in most tissues, decreases in O2
tension and pH. These changes cause relaxation of the arterioles and
precapillary sphincters. Increases in CO2 tension and osmolality
also dilate the vessels. The direct dilator action of CO2 is most
pronounced in the skin and brain. The neurally mediated vasoconstrictor effects
of systemic as opposed to local hypoxia and hypercapnia are discussed below. A
rise in temperature exerts a direct vasodilator effect, and the temperature
rise in active tissues (due to the heat of metabolism) may contribute to the
vasodilation. K+ is another substance that accumulates locally, has
demonstrated dilator activity, and probably plays a role in the dilation that
occurs in skeletal muscle. Lactate may also contribute to the dilation. In
injured tissues, histamine released from damaged cells increases capillary
permeability. Thus, it is probably responsible for some of the swelling in
areas of inflammation. Adenosine may play a vasodilator role in cardiac muscle
but not in skeletal muscle. It also inhibits the release of norepinephrine.
Localized
Vasoconstriction
Injured arteries and
arterioles constrict strongly. The constriction appears to be due in part to
the local liberation of serotonin from platelets that stick to the vessel wall
in the injured area (see Chapter 27). Injured veins also constrict.
A drop in tissue
temperature causes vasoconstriction, and this local response to cold plays a
part in temperature regulation (see Chapter 14).
SUBSTANCES
SECRETED BY THE ENDOTHELIUM
Endothelial
Cells
As noted in Chapter 30, the endothelial cells make up a large and
important organ. This organ secretes many growth factors and vasoactive
substances. The vasoactive substances include prostaglandins and thromboxanes,
nitric oxide, and endothelins.
Prostacyclin
& Thromboxane A2
Prostacyclin is
produced by endothelial cells and thromboxane A2 by platelets from
their common precursor arachidonic acid via the cyclooxygenase pathway (see Figure 17-33). Thromboxane A2 promotes platelet
aggregation and vasoconstriction, whereas prostacyclin inhibits platelet
aggregation and promotes vasodilation. The balance between platelet thromboxane
A2 and prostacyclin fosters localized platelet aggregation and
consequent clot formation (see Chapter 27) while preventing excessive extension of the clot
and maintaining blood flow around it.
The thromboxane A2-prostacyclin
balance can be shifted toward prostacyclin by administration of low doses of
aspirin. Aspirin produces irreversible inhibition of cyclooxygenase by
acetylating a serine residue in its active site. Obviously, this reduces
production of both thromboxane A2 and prostacyclin. However,
endothelial cells produce new cyclooxygenase in a matter of hours whereas
platelets cannot manufacture the enzyme, and the level rises only as new
platelets enter the circulation. This is a slow process because platelets have
a half-life of about 4 days. Therefore, administration of small amounts of
aspirin for prolonged periods reduces clot formation and has been shown to be
of value in preventing myocardial infarctions, unstable angina, transient
ischemic attacks, and stroke.
Endothelium-Derived
Relaxing Factor
A chance observation 2
decades ago led to the discovery that the endothelium plays a key role in
vasodilation. Many different stimuli act on the endothelial cells to produce endothelium-derived
relaxing factor (EDRF), a substance that is now known to be nitric oxide
(NO). NO is synthesized from arginine (Figure 31-1) in a reaction catalyzed by nitric oxide synthase
(NO synthase, NOS). Three isoforms of NOS have been identified: NOS 1, found in
the nervous system; NOS 2, found in macrophages and other immune cells; and NOS
3, found in endothelial cells. NOS 1 and NOS 3 are activated by agents that
increase intracellular Ca2+ concentration, including the
vasodilators acetylcholine and bradykinin. The NOS in immune cells is not
induced by Ca2+ but is activated by cytokines. The NO that is formed
in the endothelium diffuses to smooth muscle cells, where it activates soluble
guanylyl cyclase, producing cGMP (Figure 31-1), which in turn mediates the relaxation of
vascular smooth muscle. NO is inactivated by hemoglobin.
Adenosine, ANP, and
histamine via H2 receptors produce relaxation of vascular smooth
muscle that is independent of the endothelium. However, acetylcholine,
histamine via H1 receptors, bradykinin, VIP, substance P, and some
other polypeptides act via the endothelium, and various vasoconstrictors that
act directly on vascular smooth muscle would produce much greater constriction
if they did not simultaneously cause the release of NO. When flow to a tissue
is suddenly increased by arteriolar dilation, the large arteries to the tissue
also dilate. This flow-induced dilation is due to local release of NO. Products
of platelet aggregation also cause release of NO, and the resulting
vasodilation helps keep blood vessels with an intact endothelium patent. This
is in contrast to injured blood vessels, where the endothelium is damaged at
the site of injury and platelets therefore aggregate and produce
vasoconstriction.
Further evidence for a
physiologic role of NO is the observation that when various derivatives of
arginine that inhibit NO synthase are administered to experimental animals,
there is a prompt rise in blood pressure. This suggests that tonic release of
NO is necessary to maintain normal blood pressure.
NO is also involved in vascular remodeling and
angiogenesis, and NO may be involved in the pathogenesis of atherosclerosis. It
is interesting in this regard that some patients with heart transplants develop
an accelerated form of atherosclerosis in the vessels of the transplant, and
there is reason to believe that this is triggered by endothelial damage.
Nitroglycerin and other nitrovasodilators that are of great value in the
treatment of angina act by stimulating guanylyl cyclase in the same manner as
NO does.
There is good evidence
that penile erection is produced by release of NO, with consequent vasodilation
and engorgement of the corpora cavernosa.
Other
Functions of NO
It has become almost
commonplace to discover a compound that plays an important role in
cardiovascular regulation and then learn that it is produced in other systems
and has additional diverse functions. This is true, for example, of angiotensin
II (see Chapter 24) and the endothelins (see below). It is also true
of NO. NO is present in the brain, and, acting via cGMP, it is important in
brain function (see Chapter 4). It is necessary for the cytotoxic activity of
macrophages, including their ability to kill cancer cells. In the
gastrointestinal tract, it is a major dilator of smooth muscle. Other functions
of NO are mentioned in other parts of this book.
The production of CO
from heme is shown in Figure 4-33. HO2, the enzyme that catalyzes the reaction, is
present in cardiovascular tissues, and there is evidence that CO as well as NO
produces local dilation in blood vessels.
Endothelins
Endothelial cells also
produce endothelin-1, one of the most potent vasoconstrictor agents yet
isolated. Endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3) are
the members of a family of three similar 21-amino-acid polypeptides (Figure 31-2). Each is encoded by a different gene. The unique
structure of the endothelins resembles that of the sarafotoxins, polypeptides
found in the venom of a snake, the Israeli burrowing asp.
Endothelin-1
In endothelial cells,
the product of the endothelin-1 gene is processed to a 39-amino-acid
prohormone, big endothelin-1, which has about 1% of the activity of
endothelin-1. The prohormone is cleaved at a Trp-Val bond to form endothelin-1
by endothelin-converting enzyme. There is a family of these enzymes,
apparently related to the cleavage of big endothelin-2 and big endothelin-3 as
well as big endothelin-1. Small amounts of big endothelin-1 and endothelin-1
are secreted into the blood, but for the most part, they are secreted into the
media of blood vessels and act in a paracrine fashion.
Two different endothelin
receptors have been cloned, both of which are coupled via G proteins to
phospholipase C. The ETA receptor, which is specific for
endothelin-1, is found in many tissues and mediates the vasoconstriction
produced by endothelin-1. The ETB receptor responds to all three
endothelins, and is coupled to Gi. It may mediate vasodilation, and
it appears to mediate the developmental effects of the endothelins (see below).
Regulation
of Secretion
Endothelin-1 is not
stored in secretory granules, and most regulatory factors alter the
transcription of its gene, with changes in secretion occurring promptly
thereafter.
Cardiovascular
Functions
As noted above,
endothelin-1 appears to be primarily a local, paracrine regulator of vascular
tone. Big endothelin-1 and endothelin-1 are both present in the circulation.
However, they are not increased in hypertension, and in mice in which one
allele of the endothelin-1 gene is knocked out, blood pressure is actually
elevated rather than reduced. The concentration of circulating endothelin-1 is
elevated in congestive heart failure and after myocardial infarction, so it may
play a role in the pathophysiology of these diseases.
Other
Functions of Endothelins
Endothelin-1 is found
in the brain and kidneys as well as the endothelial cells. Endothelin-2 is
produced primarily in the kidneys and intestine. Endothelin-3 is present in the
blood and is found in high concentrations in the brain. It is also found in the
kidneys and gastrointestinal tract. In the brain, endothelins are abundant and,
in early life, are produced by both astrocytes and neurons. They are found in
the dorsal root ganglia, ventral horn cells, the cortex, the hypothalamus, and
cerebellar Purkinje cells. They also play a role in regulating transport across
the blood-brain barrier. There are endothelin receptors on mesangial cells, and
the polypeptide presumably produces mesangial cell-mediated decreases in the
glomerular filtration rate.
Mice that have both
alleles of the endothelin-1 gene deleted have severe craniofacial abnormalities
and die of respiratory failure at birth. They also have megacolon
(Hirschsprung's disease), apparently because the cells that normally form the
myenteric plexus fail to migrate to the distal colon. In addition, endothelins
play a role in closing the ductus arteriosus at birth.
SYSTEMIC
REGULATION BY HORMONES
Many circulating
hormones affect the vascular system. The vasodilator hormones include kinins,
VIP, and ANP. Circulating vasoconstrictor hormones include vasopressin,
norepinephrine, epinephrine, and angiotensin II.
Kinins
Two related vasodilator
peptides called kinins are found in the body. One is the nonapeptide bradykinin,
and the other is the decapeptide lysylbradykinin, also known as kallidin.
Lysylbradykinin can be converted to bradykinin by aminopeptidase. Both peptides
are metabolized to inactive fragments by kininase I, a carboxypeptidase
that removes the carboxyl terminal Arg. In addition, the
dipeptidylcarboxypeptidase kininase II inactivates bradykinin and
lysylbradykinin by removing Phe-Arg from the carboxyl terminal. Kininase II is
the same enzyme as angiotensin-converting enzyme, which removes His-Leu
from the carboxyl terminal end of angiotensin I.
Bradykinin and
lysylbradykinin are formed from two precursor proteins, high-molecular-weight
kininogen and low-molecular-weight kininogen. They are formed by
alternative splicing of a single gene located on chromosome 3. The biologic
activities of bradykinin and lysylbradykinin are generally similar, and it is
not known why two types are produced.
Proteases called kallikreins
release the peptides from their precursors. They are produced in humans by a
family of three genes located on chromosome 19. There are two types of
kallikreins: plasma kallikrein, which circulates in an inactive form,
and tissue kallikrein, which appears to be located primarily on the
apical membranes of cells concerned with transcellular electrolyte transport.
Tissue kallikrein is found in many tissues, including sweat and salivary
glands, the pancreas, the prostate, the intestine, and the kidneys. Tissue
kallikrein acts on high-molecular-weight kininogen and low-molecular-weight
kininogen to form lysylbradykinin. When activated, plasma kallikrein acts on
high-molecular-weight kininogen to form bradykinin.
Inactive plasma
kallikrein (prekallikrein) is converted to the active form, kallikrein,
by active factor XII, the factor which initiates the intrinsic blood clotting
cascade. Kallikrein also activates factor XII in a positive feedback loop, and high-molecular-weight
kininogen has a factor XII-activating action.
The actions of the
kinins resemble those of histamine. They are primarily tissue hormones,
although small amounts are also found in the circulating blood. They cause
contraction of visceral smooth muscle, but they relax vascular smooth muscle
via NO, lowering blood pressure. They also increase capillary permeability,
attract leukocytes, and cause pain upon injection under the skin. They are
formed during active secretion in sweat glands, salivary glands, and the
exocrine portion of the pancreas, and they are probably responsible for the
increase in blood flow when these tissues are actively secreting their
products. They are present in the kidneys, where their function is uncertain.
Two bradykinin
receptors, B1 and B2, have been identified. Their amino
acid residues are 36% identical, and both are serpentine receptors coupled to G
proteins. The B1 receptor may mediate the pain-producing effects of
the kinins, but little is known about its distribution and function. The B2
receptor has strong homology to the H2 receptor and is found in many
different tissues.
Adrenomedullin
Adrenomedullin (AM) is a depressor polypeptide first isolated from pheochromocytoma cells.
Its prohormone is also the source of another depressor polypeptide,
proadrenomedullin amino terminal 20 peptide (PAMP). AM also inhibits
aldosterone secretion in salt-depleted animals and appears to produce its
depressor effect by increasing production of NO. PAMP appears to act by inhibiting
peripheral sympathetic nerve activity. Both AM and PAMP are found in plasma and
in many tissues in addition to the adrenal medulla, including the kidney and
the brain. However, the role, if any, of AM and PAMP in cardiovascular control
is still unknown.
Natriuretic
Hormones
The atrial natriuretic
peptide (ANP) secreted by the heart antagonizes the action of various
vasoconstrictor agents and lowers blood pressure, but its exact role in the
regulation of the circulation is still unsettled. The natriuretic Na+-K+
ATPase inhibitor, which is now thought to be endogenously produced ouabain,
apparently raises rather than lowers blood pressure.
Circulating
Vasoconstrictors
Vasopressin is a potent
vasoconstrictor, but when it is injected in normal individuals, there is a
compensating decrease in cardiac output, so that there is little change in
blood pressure.
Norepinephrine has a
generalized vasoconstrictor action, whereas epinephrine dilates the vessels in
skeletal muscle and the liver. The relative unimportance of circulating
norepinephrine, as opposed to norepinephrine released from vasomotor
nerves, where the cardiovascular actions
of catecholamines are discussed in detail.
The octapeptide
angiotensin II has a generalized vasoconstrictor action. It is formed from
angiotensin I liberated by the action of renin from the kidney on circulating
angiotensinogen. Its formation is increased because renin secretion is
increased when the blood pressure falls or ECF volume is reduced, and it helps
maintain blood pressure. Angiotensin II also increases water intake and
stimulates aldosterone secretion, and increased formation of angiotensin II is
part of a homeostatic mechanism that operates to maintain ECF volume. In
addition, there are renin-angiotensin systems in many different organs, and
there may be one in the walls of blood vessels. Angiotensin II produced in
blood vessel walls could be important in some forms of clinical hypertension.
Urotensin-II, a polypeptide first isolated from the spinal cord of fish, is present
in human cardiac and vascular tissue. It is one of the most potent mammalian
vasoconstrictors known, but its physiologic role is still uncertain.
SYSTEMIC
REGULATION BY THE NERVOUS SYSTEM
Neural
Regulatory Mechanisms
Although the arterioles
and the other resistance vessels are most densely innervated, all blood vessels
except capillaries and venules contain smooth muscle and receive motor nerve
fibers from the sympathetic division of the autonomic nervous system. The
fibers to the resistance vessels regulate tissue blood flow and arterial
pressure. The fibers to the venous capacitance vessels vary the volume of blood
"stored" in the veins. The innervation of most veins is sparse, but
the splanchnic veins are well innervated. Venoconstriction is produced by
stimuli that also activate the vasoconstrictor nerves to the arterioles. The
resultant decrease in venous capacity increases venous return, shifting blood
to the arterial side of the circulation.
Innervation
of the Blood Vessels
Noradrenergic fibers
end on vessels in all parts of the body. The noradrenergic fibers are
vasoconstrictor in function. In addition to their vasoconstrictor innervation,
the resistance vessels of the skeletal muscles are innervated by vasodilator
fibers, which, although they travel with the sympathetic nerves, are
cholinergic (the sympathetic vasodilator system.) There is some evidence
that blood vessels in the heart, lungs, kidneys, and uterus also receive a
cholinergic innervation. Bundles of noradrenergic and cholinergic fibers form a
plexus on the adventitia of the arterioles. Fibers with multiple varicosities
extend from this plexus to the media and end primarily on the outer surface of
the smooth muscle of the media without penetrating it. Transmitters reach the
inner portions of the media by diffusion, and current spreads from one smooth
muscle cell to another via gap junctions.
There is no tonic
discharge in the vasodilator fibers, but the vasoconstrictor fibers to most
vascular beds have some tonic activity. When the sympathetic nerves are cut (sympathectomy),
the blood vessels dilate. In most tissues, vasodilation is produced by
decreasing the rate of tonic discharge in the vasoconstrictor nerves, although
in skeletal muscles it can also be produced by activating the sympathetic
vasodilator system.
Nerves containing
polypeptides are found on many blood vessels. The cholinergic nerves also
contain VIP, which produces vasodilation. The noradrenergic postganglionic
sympathetic nerves also contain neuropeptide Y, which is a vasoconstrictor.
Substance P and CGRPα, which produce vasodilation, are found in sensory
nerves near blood vessels.
Afferent impulses in
sensory nerves from the skin are relayed antidromically down branches of the
sensory nerves that innervate blood vessels, and these impulses cause release
of substance P from the nerve endings. Substance P causes vasodilation and
increased capillary permeability. This local neural mechanism is called the axon
reflex (see Figure 32-17). Other cardiovascular reflexes are integrated
in the central nervous system.
Cardiac
Innervation
Impulses in the
noradrenergic sympathetic nerves to the heart increase the cardiac rate
(chronotropic effect) and the force of cardiac contraction (inotropic effect).
They also inhibit the effects of vagal stimulation, probably by release of
neuropeptide Y, which is a cotransmitter in the sympathetic endings. Impulses
in the cholinergic vagal cardiac fibers decrease the heart rate. There is a
moderate amount of tonic discharge in the cardiac sympathetic nerves at rest,
but there is a good deal of tonic vagal discharge (vagal tone) in humans
and other large animals. When the vagi are cut in experimental animals, the
heart rate rises, and after the administration of parasympatholytic drugs such
as atropine, the heart rate in humans increases from 70, its normal resting
value, to 150-180 beats/min because the sympathetic tone is unopposed. In
humans in whom both noradrenergic and cholinergic systems are blocked, the
heart rate is approximately 100.
Vasomotor
Control
The sympathetic nerves
that constrict arterioles and veins and increase heart rate and stroke volume
discharge in a tonic fashion, and blood pressure is adjusted by variations in
the rate of this tonic discharge. Spinal reflex activity affects blood
pressure, but the main control of blood pressure is exerted by groups of
neurons in the medulla oblongata that are sometimes called collectively the vasomotor
area or vasomotor center. Neurons that mediate increased sympathetic
discharge to blood vessels and the heart project directly to sympathetic
preganglionic neurons in the intermediolateral gray column (IML) of the spinal
cord. On each side, the cell bodies of these neurons are located near the pial
surface of the medulla in the rostral ventrolateral medulla (RVLM). Their axons
course dorsally and medially and then descend in the lateral column of the
spinal cord to the IML. They contain PNMT, but it appears that the excitatory
transmitter they secrete is glutamate rather than epinephrine.
Impulses reaching the
medulla also affect the heart rate via vagal discharge to the heart. The
neurons from which the vagal fibers arise are in the dorsal motor nucleus of
the vagus and the nucleus ambiguus.
When vasoconstrictor
discharge is increased, there is increased arteriolar constriction and a rise
in blood pressure. Venoconstriction and a decrease in the stores of blood in
the venous reservoirs usually accompany these changes, although changes in the
capacitance vessels do not always parallel changes in the resistance vessels.
Heart rate and stroke volume are increased because of activity in the
sympathetic nerves to the heart, and cardiac output is increased. There is
usually an associated decrease in the tonic activity of vagal fibers to the
heart. Conversely, a decrease in vasomotor discharge causes vasodilation, a
fall in blood pressure, and an increase in the storage of blood in the venous
reservoirs. There is usually a concomitant decrease in heart rate, but this is
mostly due to stimulation of the vagal innervation of the heart.
Afferents
to the Vasomotor Area
The afferents that
converge on the vasomotor area include not only the very important fibers from
arterial and venous baroreceptors but also fibers from other parts of the
nervous system and from the carotid and aortic chemoreceptors. In addition,
some stimuli act directly on the vasomotor area.
There are descending
tracts to the vasomotor area from the cerebral cortex (particularly the limbic
cortex) that relay in the hypothalamus. These fibers are responsible for the
blood pressure rise and tachycardia produced by emotions such as sexual
excitement and anger. The connections between the hypothalamus and the
vasomotor area are reciprocal, with afferents from the brain stem closing the
loop.
Inflation of the lungs
causes vasodilation and a decrease in blood pressure. This response is mediated
via vagal afferents from the lungs that inhibit vasomotor discharge. Pain
usually causes a rise in blood pressure via afferent impulses in the reticular
formation converging on the vasomotor area. However, prolonged severe pain may
cause vasodilation and fainting.
Somatosympathetic
Reflex
Pain causes increased
arterial pressure, and activity in afferents from exercising muscles probably
exerts a similar pressor effect via the C1 neurons in the rostral ventrolateral
medulla. The pressor response to stimulation of somatic afferent nerves is
called the somatosympathetic reflex.
Baroreceptors
The baroreceptors
are stretch receptors in the walls of the heart and blood vessels. The carotid
sinus and aortic arch receptors monitor the arterial circulation.
Receptors are also located in the walls of the right and left atria at the
entrance of the superior and inferior venae cavae and the pulmonary veins, as
well as in the pulmonary circulation. These receptors in the low-pressure part
of the circulation are referred to collectively as the cardiopulmonary
receptors. The baroreceptors are stimulated by distention of the structures in
which they are located, and so they discharge at an increased rate when the
pressure in these structures rises. Their afferent fibers pass via the
glossopharyngeal and vagus nerves to the medulla. Most of them end in the
nucleus of the tractus solitarius (NTS), and the excitatory transmitter they
secrete is probably glutamate. There are excitatory, presumably glutaminergic,
projections from the NTS to the caudal and intermediate ventrolateral medulla,
where they apparently stimulate GABA-secreting inhibitory neurons that project
to the rostral ventrolateral medulla. There are also excitatory projections,
probably polyneuronal, from the NTS to the vagal motor neurons in the dorsal
motor nucleus and the nucleus ambiguus. Thus, increased baroreceptor discharge inhibits
the tonic discharge of the vasoconstrictor nerves and excites the vagal
innervation of the heart, producing vasodilation, venodilation, a drop in blood
pressure, bradycardia, and a decrease in cardiac output.
Carotid
Sinus & Aortic Arch
The carotid sinus is a
small dilation of the internal carotid artery just above the bifurcation of the
common carotid into external and internal carotid branches. Baroreceptors are
located in this dilation. They are also found in the wall of the arch of the
aorta. The receptors are located in the adventitia of the vessels. They are
extensively branched, knobby, coiled, and intertwined ends of myelinated nerve
fibers that resemble Golgi tendon organs. Similar receptors have been found in
various other parts of the large arteries of the thorax and neck in some
species. The afferent nerve fibers from the carotid sinus and carotid body form
a distinct branch of the glossopharyngeal nerve, the carotid sinus nerve,
but the fibers from the aortic arch form a separate distinct branch of the
vagus only in the rabbit. The carotid sinus nerves and vagal fibers from the
aortic arch are commonly called the buffer nerves.
Buffer
Nerve Activity
At normal blood
pressure levels, the fibers of the buffer nerves discharge at a low rate (Figure 31-10). When the pressure in the sinus and aortic arch
rises, the discharge rate increases; and when the pressure falls, the rate
declines.
When one carotid sinus
of a monkey is isolated and perfused and the other baroreceptors are
denervated, there is no discharge in the afferent fibers from the perfused sinus
and no drop in the animal's arterial pressure or heart rate when the perfusion
pressure is below
The carotid receptors
respond both to sustained pressure and to pulse pressure. A decline in carotid
pulse pressure without any change in mean pressure decreases the rate of
baroreceptor discharge and provokes a rise in blood pressure and tachycardia.
The receptors also respond to changes in pressure as well as steady pressure;
when the pressure is fluctuating, they sometimes discharge during the rises and
are silent during the falls at mean pressures at which if there were no
fluctuations, there would be a steady discharge.
The aortic receptors
have not been studied in such great detail, but there is no reason to believe
that their responses differ significantly from those of the receptors in the
carotid sinus.
From the foregoing
discussion, it is apparent that the baroreceptors on the arterial side of the
circulation, their afferent connections to the vasomotor and cardioinhibitory
areas, and the efferent pathways from these areas constitute a reflex feedback
mechanism that operates to stabilize the blood pressure and heart rate. Any
drop in systemic arterial pressure decreases the inhibitory discharge in the
buffer nerves, and there is a compensatory rise in blood pressure and cardiac
output. Any rise in pressure produces dilation of the arterioles and decreases
cardiac output until the blood pressure returns to its previous normal level.